Acute Exacerbation Of Ulcerative Colitis Research Articles

Gut microbiota-derived 12-ketolithocholic acid suppresses the IL-17A secretion from colonic group 3 innate lymphoid cells to prevent the acute exacerbation of ulcerative colitis

ABSTRACT Intestinal microbiota dysbiosis and metabolic disruption are well-known as the primary triggers of ulcerative colitis (UC). However, their role in regulating the group 3 innate lymphoid cells (ILC3s), which are essential for intestinal health, remains unexplored during the development of disease severity. Here, our results showed that the microbiota structure of patients with severe UC (SUCs) differed from those with mild UC (MiUCs), moderate UC (MoUCs), and healthy controls (HCs). Microbes producing secondary bile acids (SBAs) and SBAs decreased with the aggravation of UC, and a strong positive correlation existed between them. Next, fecal microbiota transfer was used to reproduce the human-derived microbiota in mice and decipher the microbiota-mediated inflammatory modulation during an increase in disease severity. Mice receiving SUC-derived microbiota exhibited enhancive inflammation, a lowered percentage of ILC3s, and the down-regulated expressions of bile acid receptors, including vitamin D receptor (VDR) and pregnane X receptor (PXR), in the colon. Similar to clinical results, SBA-producing microbes, deoxycholic acids (DCA), and 12-ketolithocholic acids (12-KLCA) were diminished in the intestine of these recipients. Finally, we compared the therapeutic potential of DCA and 12-KLCA in preventing colitis and the regulatory mechanisms mediated by ILC3s. 12-KLCA but not DCA represented a strong anti-inflammatory effect associated with the higher expression of VDR and the lower secretion of IL-17A from colonic ILC3s. Collectively, these findings provide new signatures for monitoring the acute deterioration of UC by targeting gut microbiota and bile acid metabolism and demonstrate the therapeutic and preventive potential of a novel microbiota-derived metabolite, 12-KLCA.

Successful pregnancy of a patient with primary sclerosing cholangitis awaiting liver transplantation

In women, primary sclerotising cholangitis (PSC) associated with ulcerative colitis and intrahepatic cholestasis is a rare disease. To date, there are no data from Hungary on the fertility and pregnancy outcome of women with this chronic liver disease. Our aim is to present the favorable pregnancy outcome of a woman with PSC associated with ulcerative colitis, intrahepatic cholestasis and postpartum colectomy, and review of the literature. A young nulligravida was first diagnosed with ulcerative colitis. Five years later, PSC developed with progressive fibrosis and cholestasis necessitating liver transplantation. While on waiting list, spontaneous conception occurred. Except for pregnancy-induced hypertension, pregnancy uneventfully progressed until the third trimester when 8 g oral cholestyramine/day was administered to lower high maternal (over 100 μmol/L) total bile acid (TBA) level. In the 36th week of gestation acute exacerbation of ulcerative colitis resulted in maternal fever and chorioamnionitis leading to fetal distress. Elective delivery of the eutrophic neonate followed by emergency cesarean section. In the early puerperium, colitis progressed to septic pancolitis resistant to medical treatment. 12 days after laparoscopic subtotal colectomy, the patient was discharged in good health condition. 3 months later, ileostomy was closed and she got back on the transplantation waiting list. Our data correspond with previous reports and suggest that women with PSC with underlying ulcerative colitis and cholestasis have a good chance for favorable pregnancy outcome. However, both PSC and underlying colitis might progress during pregnancy and puerperium. Oral cholestyramin is an effective and safe treatment for high maternal TBA levels. Orv Hetil. 2023; 164(6): 234-240.

S2716 CMV in IBD: An Innocent Bystander, or Active Pathogen?

Introduction: Ulcerative Colitis (UC) is a gastrointestinal inflammatory disease that affects over 6 million people worldwide. Clinical manifestations of UC such as bloody diarrhea and abdominal pain can often mimic an infectious colitis, such as cytomegalovirus (CMV) colitis. Often a silent infection, CMV has a worldwide seroprevalence of 83%. We present an interesting case of a UC patient with biopsy positive CMV colitis, who symptomatically improved on steroids and mesalamine alone. Case Description/Methods: A 66 year old African American female with a history of well-controlled UC was evaluated for acute onset bloody diarrhea and abdominal pain. Following negative stool studies for infection, the patient underwent colonoscopic evaluation. Preliminary imaging and results demonstrated a left-sided UC flare extending from the rectum to the splenic flexure. The patient was started on pulse dose steroids with instructions to taper as an outpatient and experienced resolution of symptoms. Biopsy revealed CMV with subsequent serologic testing showing a CMV viral load of < 390 cpy/mL, IgM level of 45.4 AU/mL and negative IgG levels. Interestingly, the patient's acute gastrointestinal symptoms resolved with glucocorticoid treatment. Discussion: CMV reactivation is common in patients with moderate to severe UC. Symptoms of diarrhea, bloody stool, abdominal pain and complications such as megacolon, fulminant colitis and perforation often overlap in both CMV and UC. Endoscopic evaluation can provide a more definitive means of differentiating CMV colitis from an acute exacerbation of UC, however, may not be able to be quickly performed before complications arise. There has been much debate on the role of CMV in UC and whether it is an active pathogen contributing to the inflammatory state or simply a surrogate marker for disease severity. Multiple studies have demonstrated an association of CMV antigenemia with endoscopically significant severe UC. In such patients, after detection of CMV in the colon with biopsy, treatment with antiviral therapy and withdrawal of immunosuppressive agents would be expected to induce clinical response. Continuation of immunosuppressive therapies was associated with adverse events such as fulminant colitis and colectomy. (Figure) Differentiating an active CMV infection versus a UC flare can be challenging given the wide overlap of symptoms. Colonoscopic evaluation is important in supplementing a diagnosis with histopathological confirmation of CMV and can help guide treatment.Figure 1.: Inflammation characterized by friability, loss of vascularity, mucous, pseudopolyps and deep ulcerations was found in a continuous and circumferential pattern in the terminal ileum (1,2), hepatic flexure (3), transverse colon (4,5,6), descending colon (7,8), sigmoid colon (9,10,11), and rectum (12,13,14). This was graded as Mayo Score 3 (severe, with spontaneous bleeding, ulcerations).

Sudden-Onset Polyposis in Pediatric Patients With Ulcerative Colitis.

To the Editors: Inflammatory polyps may develop in 10% to 20% patients with inflammatory bowel disease (IBD).1 However, such patients are mostly adults, and polyps rarely develop in children. Filiform polyps are extremely rare in children with ulcerative colitis (UC).2 Herein, we present a case of sudden-onset filiform polyposis during UC treatment in an 11-year-old girl. Low-grade dysplasia was histopathologically confirmed in another single polyp; therefore, this case underlines the importance of evaluating the heterogeneity of inflammatory polyps in pediatric patients with UC and follow-up of such patients. A 9-year-old girl presented with severe anemia and hematochezia. Her blood test findings were as follows: white blood cell count, 12 620/μL (eosinophils, 10.3%); hemoglobin, 6.4 g/dL. Her QuantiFERON-TB test result was negative; furthermore, she tested negative for cytomegalovirus, herpes simplex virus, fluorescent antinuclear antibody, Clostridium difficile, and antineutrophil cytoplasmic antibodies. Her immunoglobulin E level was 260.5 IU/mL (reference range, <158 IU/mL). Moreover, her fecal calprotectin concentration was over 6000 mg/kg. Colonoscopy showed a severe UC flare-up throughout the colon. She was initially treated with corticosteroids, azathioprine, and 5-aminosalicylic acid; however, there was no symptom improvement. After 4 months, infliximab (5 mg/kg) was administered; however, diarrhea and hematochezia persisted. Her fecal calprotectin concentration was 2000 to 5000 mg/kg. Infliximab trough level and anti-infliximab antibody were 0.1 μg/mL and 25.3 ng/mL, respectively. Therefore, infliximab was discontinued, and intermittent steroid treatment was continued with cyclosporine as the main drug. Although there was no acute exacerbation of UC, complete remission could not be achieved. Colonoscopy performed 15 months later yielded findings similar to those obtained in the previous one. After 18 months, polyps that had not been seen before suddenly appeared in the form of filiform polyposis in the transverse colon (Figure 1A). Biopsy findings revealed inflammatory polyposis (Figure 1B). A single polyp (sized approximately 3 cm) was observed in the sigmoid colon (Figure 1C); histopathological examination showed low-grade dysplasia (Figure 1D). The patient underwent diagnostic exome sequencing; APC gene mutation or other IBD- or immune deficiency–related mutations were not detected. Tumor marker levels and positron emission tomography computed tomography findings indicated no evidence of malignancy in other organs.

“Lead-Pipe Colon” of Chronic Ulcerative Colitis on Abdominal X-Ray

Lead-pipe colon is a characteristic sign of chronic ulcerative colitis typically seen on barium enema or contrast computed tomography. We present image of this condition on abdominal X-ray and highlight the importance of this sign in acute exacerbation of ulcerative colitis.

Bullous Sweet’s syndrome in a patient with ulcerative colitis: a rare case report

Bullous Sweet's syndrome is an uncommon clinical presentation of classical Sweet's syndrome, often associated with various kinds of tumors, infections, and active inflammatory bowel diseases (IBDs), namely Crohn's disease and ulcerative colitis. Only a few cases of bullous Sweet's syndrome associated with ulcerative colitis are described in the literature. We report a case of a 62-year-old female patient with acute exacerbation of ulcerative colitis associated with infiltrating purple-erythematous skin plaques, which were partly vesicular, and oral ulcerative stomatitis. Biopsy was consistent with bullous Sweet's syndrome. Treatment with betamethasone sodium phosphate, starting at 5.5 mg, followed by gradual dose tapering for 12 weeks, resulted in improvement of the ulcerative colitis and disappearance of the cutaneous lesions. Bullous Sweet's syndrome most commonly occurs in the setting of hematologic malignancies, suggesting that physicians should perform long-term screening for early diagnosis of hematological and solid malignancies.

Polymerase chain reaction for detection of mucosal cytomegalovirus infection in patients with acute ulcerative colitis.

BackgroundCytomegalovirus (CMV) infection is associated with acute exacerbations of ulcerative colitis (UC) but its clinical relevance remains uncertain. The primary aim of this study was to assess the prevalence of CMV infection in UC patients using viral polymerase chain reaction (PCR) analysis of mucosal biopsy samples. Secondary aims were to establish whether the disease was due to a primary infection or reactivation and to note associated risk factors and clinical outcomes.MethodsSince 2011, a policy of biopsy for CMV infection was adopted for severe UC patients in a large tertiary center. A retrospective review was undertaken to identify patients with mucosal biopsies for exacerbations of UC from October 2011 through January 2014.ResultsSixty biopsies for CMV PCR were obtained from 52 patients, 15 of whom were positive. In these patients, 9/9 tested were seropositive for anti-CMV IgG, while none were seropositive for anti-CMV IgM. Steroid refractory disease was a significant predictor of CMV positivity; however, there was no difference between the CMV-positive and -negative groups in rates of immunosuppression, or clinical and endoscopic severity. Six patients in the CMV-positive group received infliximab; all received concurrent antiviral therapy and did not require surgery.ConclusionsPCR of mucosal biopsies detected CMV infection due to viral reactivation in almost a third of patients with deteriorating or acute severe UC. Steroid refractory disease was significantly associated with CMV positivity, but no significant relationship was demonstrated with either disease severity or immunosuppression in our cohort. Treatment with anti-tumor necrosis factor agents was administered safely in combination with antiviral drugs.

P660 Prevalence and clinical course of cytomegalovirus colitis in Asian patients with acute exacerbation of ulcerative colitis

Background: In Inflammatory bowel disease (IBD), reactivation of human cytomegalovirus colitis (CMV) infection can occur as a result of chronic immunosuppression and local inflammation in the bowel wall [1]. CMV reactivation is common in patients with severe colitis, with a reported prevalence of 4.5–16.6% [2], and occurs more frequently in ulcerative colitis (UC) than Crohn's disease (CD), possibly due to their different cytokine profile. CMV colonic disease can exacerbate UC disease activity, and has been associated with decrease response to corticosteroids/ immunosuppressive therapy [3], higher colectomy rates [4] and longer hospitalisation stay. However, it remains controversial if anti-viral therapy alters the course of UC; there is also a lack of data on the prevalence of CMV colonic disease in Asian IBD patients. We aim to determine the prevalence of CMV colonic disease and clinical course in Asian patients with acute exacerbation of UC in Singapore, a multiracial country consisting predominantly of Chinese, Malays and Indians. Methods: Electronic records of 125 patients with ulcerative colitis (UC) who were hospitalised for acute exacerbation from 2002- October 2016 were retrospectively reviewed. Biodata, clinical presentation and treatment information was extracted. The diagnosis of CMV colonic disease was based on histological identification of CMV inclusion bodies and/or positive immune-histochemistry (IHC). The severity of UC was graded according to Truelove and Witt's criteria. Results: There were 125 (65% Male; 56% Chinese; 23% Indian, 12% Malay, 9% others) UC patients with 205 admissions to hospital. Of these, 39 patients had 78 admissions for acute exacerbation of disease activity (6% Mild, 27% Moderate, 68% Severe, 2% Fulminant). Four patients (5.1%) were diagnosed with CMV colonic disease, including 1 patient with newly diagnosed UC; of these, 3 were steroid-refractory and 2 were on long-term azathioprine, 2 had deep colonic ulcers at endoscopy and CMV DNA (colon biopsy) ranged 5400–290000 copies/mg. All patients received anti-viral therapy: 2 responded well and achieved steroid-free remission; 2 failed to respond (including 1 who failed infliximab rescue therapy) and subsequently underwent total colectomy. CMV tissue DNA load, presence of deep colonic ulcers did not predict response to treatment or clinical outcome. Conclusions: The prevalence of CMV colonic disease was 5% in Asian UC patients with acute exacerbation. Anti-viral therapy conferred benefit in only some patients who subsequently achieve steroid-free remission. Larger studies are needed to determine prognostic factors and identify subgroups that will benefit from anti-viral therapy.

Assessment of Disease Severity and Role of Cytomegalo Virus Infection in Patients with Ulcerative Colitis.

Course of Ulcerative Colitis is characterized by intermittent flares interposed between variable periods of remission. Identification of exacerbating factors and appropriate assessment of disease activity are crucial in deciding the choice of treatment. To evaluate various clinical, endoscopic and histological parameters in assessing disease activity and to find out various risk factors involved in the exacerbation of ulcerative colitis especially the role of Cytomegalo Virus (CMV) infection. It was a prospective study of patients diagnosed as ulcerative colitis presenting with acute exacerbation of symptoms (cases) and those who were in remission (controls). A detailed evaluation of the disease history including personal history, treatment compliance and clinical disease severity were noted. Investigations including blood routine, endoscopic examination with biopsy, histopathological examination and immunohistochemistry for CMV were done on the biopsy sample. A total of 58 patients with ulcerative colitis were studied which included 37 cases and 21 controls. Out of the various clinical and demographic parameters, Good treatment compliance (p =0.0003) and Perceived Stress Scale (PSS) score (p=0.0001) showed significant difference between cases and controls. Basic laboratory parameters {Haemoglobin level, Total Leucocyte Count (TLC) and Erythrocyte Sedimentation Rate (ESR)}, clinical disease severity predictors (Truelove and Witt's criteria, Mayo score and endoscopic disease severity grade) and Geboes histological scoring showed significant difference between cases and controls. The prevalence of CMV colitis in our study was only 5.4% (two cases). Clinical and endoscopic disease severity indicators can be used as predictors of histological activity in ulcerative colitis. Poor treatment compliance and stress are important risk factors for acute exacerbation of ulcerative colitis. Clinicians should be aware of the possibility of concurrent CMV infection while treating patients with acute exacerbation of ulcerative colitis not responding to the conventional management. Reduced prevalence of CMV colitis in cases of acute exacerbation of ulcerative colitis in our study may be due to the small sample size, reduced number of steroid dependent cases or reduced severity of our cases.

A Case of Kaposi's Sarcoma of the Rectum in a Homosexual Male with HIV–AIDS

Kaposi sarcoma (KS) is a locally aggressive endothelial tumor, commonly diagnosed among individuals with acquired immunodeficiency syndrome (AIDS). The most typical site of involvement by KS is the skin, but in some cases, it can also affect other tissues and organs. Most patients with gastrointestinal involvement of Kaposi's sarcoma remain asymptomatic and they are often diagnosed on endoscopy or autopsy. However, there are cases of KS mimicking ulcerative colitis (UC), whereby clinical manifestations can confuse physicians. We report a 31 y old homosexual man who presented with rectal pain and bleeding. Patient was diagnosed eight years ago with HIV/ AIDS, and despite highly active retroviral therapy, he developed extensive skin lesions. Because of expressive rectal pain and bleeding, he underwent rectoscopy, which revealed ulcerous and hemorrhagic lesions. The rectoscopic and clinical presentation mimicked acute flare of UC, which was patient initial diagnosis. Tissue samples were collected for microscopical examination. After histological, histochemical and immunhistochemical examination of the sampled tissue, KS diagnosis was confirmed. The clinical manifestations of Kaposi sarcoma can be confused with acute exacerbation of ulcerative colitis often delaying the diagnosis. Therefore, early endoscopic evaluation with adequate biopsies could help in timely diagnosis and management of gastrointestinal KS (GI-KS) in patients with HIV/AIDS, even if they do not have skin lesions.

Recent advances in inflammatory bowel disease.

Recent advances in inflammatory bowel disease.

PTH-065 The impact of changes to the nice guideline on the use of biologic agents in ulcerative colitis in a uk district general hospital: Abstract PTH-065 Table 1

<h3>Introduction</h3> After pressure from patient and clinical groups NICE have reversed their position on biologics^1,2in subacute ulcerative colitis (UC) and it will be available to patients in 2015. <h3>Method</h3> A retrospective review of the use of infliximab for the treatment of UC in a single centre DGH between 2011 and 2014. <h3>Results</h3> Ten patients received infliximab for acute severe UC and ten for subacute UC. In the 12 months pre-infliximab these patients received 40 courses of prednisolone between them (Table 1). All subacute patients had received immunomodulators. All subacute patients had a partial or complete clinical (MAYO score) and biochemical response following infliximab induction, compared to 50% of the acute severe group. Two patients remain on long-term infliximab and in remission. Colectomy was required within 12 months for 55.6% of patients with acute severe disease and 44.4% of those with subacute activity. 60% of the remaining subacute patients (n = 3) have received steroids since infliximab. <h3>Conclusion</h3> NICE change of position²echos current practice in our centre and with the change in guidelines we may hope to see a reduction in steroid use prior to the use of biological treatment. However the long term success of infliximab in UC is limited. Subacute patients showed better immediate outcomes in terms of biochemical and clinical response, but at 12 months, outcomes were similar in both groups. Work is needed to identify the likely responders to make its use cost effective and evidence based guidance is needed on the clinical benefits of switching to alternative biological agents if infliximab fails. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Infliximab for acute exacerbations of ulcerative colitis. Available at: https://www.nice.org.uk/guidance/ta163. Accessed on 07/01/2015 Ulcerative colitis (moderate, severe) – infliximab (review TA140), adalimumab (review TA262) &amp; golimumab (2nd line) [ID695]. Available at: http://www.nice.org.uk/Guidance/InDevelopment/GID-TAG357. Accessed on 23/02/2015

PTH-254 Unexpected findings in magnetic resonance enterography (MRE) and their clinical significance: Abstract PTH-254 Table 1

The clinical and pathological features of five sporadic cases of enteric infection caused by Escherichia coli O157 (enterohaemorrhagic or Vero cytotoxin-producing E coli showed a range of features. These included one case with pseudomembranous colitis, one with an acute exacerbation of ulcerative colitis, and three with enterocolitis. Diagnostic difficulties encountered initially in four of the five cases were finally resolved by correlating the results of microbiological with histopathological investigations. In view of the heterogeneity of clinical and histological signs and symptoms, it is concluded that all patients with abdominal pain and diarrhoea or rectal bleeding should have early microbiological investigation.

Ulcerative Colitis and Limb Loss: A Case Report

Introduction: Protein C is a precursor of a vitamin K-dependent serine protease, which is activated by thrombin in the presence of endothelial cofactor, thrombomodulin and endothelial cell protein C receptor. Case Presentation: A 33-year old woman with acute exacerbation of ulcerative colitis was found to have protein C deficiency (serum protein C activity estimated as 35% of the normal activity). Protein C deficiency was diagnosed after the onset of several arterial thromboemboli complications (brachiocephalic and popliteal artery thrombosis) during her hospital admission for exacerbation of ulcerative colitis (UC). Therefore, upper limb below elbow and lower limb below knee amputation were performed for her. Conclusions: After total proctocolectomy, serum protein C activity remained as 35% of the normal activity, so the patient used warfarin as lifelong anticoagulant. Investigation of other family members revealed normal thrombophilia screening tests.

Randomized clinical trial: Atorvastatin versus placebo in patients with acute exacerbation of mild to moderate ulcerative colitis

Statins are known to possess pleiotropic anti-inflammatory properties which have been evaluated for clinical benefits in a number of disorders. Studies have demonstrated beneficial actions of statins in experimental models of colitis. Clinical evidence in acute exacerbation of ulcerative colitis (UC) is lacking. This study aims to assess the efficacy and safety of add-on atorvastatin in mild to moderately severe acute exacerbation of UC. Patients with acute exacerbation of UC were randomized to receive either atorvastatin (20 mg) or matching placebo once daily orally for 8 weeks in addition to the standard therapy. Clinical efficacy was assessed by using partial Mayo score (PMS). Previously diagnosed 64 cases of UC presenting with mild to moderately severe acute exacerbation were randomized to receive either atorvastatin of 20 mg or placebo. Mean PMS increased by 1.5 points and decreased by 0.31 points in atorvastatin and placebo groups, respectively, at 8 weeks compared to the baseline values (p = 0.04). Eight (25 %) and 13 (40.6 %) patients attained the primary outcome criteria for clinical improvement in the atorvastatin and placebo arms, respectively (p = 0.18). Fifteen (46.8 %) patients in the atorvastatin group and no patient in the placebo group had ≥2 point increase in PMS after 8 weeks (p < 0.001). Atorvastatin therapy in acute exacerbation of UC may not be associated with beneficial effects. Paradoxical increase in disease activity may be seen in some patients. However, these findings need to be substantiated in larger studies.

Cost-Effectiveness of Infliximab for the Treatment of Acute Exacerbations of Ulcerative Colitis in the Netherlands.

IntroductionInfliximab is registered for the treatment of moderate-to-severe active ulcerative colitis (UC) adult patients who have had an inadequate response, or are intolerant, or have medical contraindications to therapy including corticosteroids and 5-aminosalicylates or thiopurines (6-mercaptopurine [6-MP] or azathioprine [AZA]). The authors estimate the costs and effects and evaluate the cost-effectiveness of infliximab at the licensed dose of 5 mg/kg versus cyclosporine or surgery for the treatment of adult Dutch patients hospitalized with acute exacerbations of UC, refractory to intravenous steroids.MethodAn existing decision analytical model was updated to simulate disease progression of hospitalized UC patients in the Netherlands, refractory to intravenous corticosteroids, and to estimate the costs and benefits associated with infliximab compared to cyclosporine and surgery over a 1-year time horizon. Colectomy rates were derived from infliximab and cyclosporine randomized trials and synthesized using multiple treatment comparison methods. The utility estimates associated with health states of ulcerative colitis patients were obtained from the literature. Resource use and drug use frequencies as well as unit costs were obtained from Dutch sources. The primary effectiveness measure used in the analysis was quality-adjusted life years (QALYs).ResultsFor a typical UC patient with body weight of 70 kg, the costs of treatment with infliximab, cyclosporine, and surgery over a 1-year treatment period were €17,062, €14,784, €13,979, respectively. The associated numbers of QALYs were 0.80, 0.70, and 0.58 for infliximab, cyclosporine, and surgery respectively. The incremental cost-effectiveness ratio for infliximab was €24,277 per QALY gained compared to cyclosporine, and €14,639 per QALY gained compared to surgery.ConclusionsInfliximab induction regimen appears to be a cost-effective treatment option in comparison to cyclosporine and surgery for hospitalized patients with acute exacerbations of UC, refractory to intravenous corticosteroids in the Netherlands.

The Surgical Management of Active Ulcerative Colitis Complicated by Clostridium difficile Infection

IntroductionClostridium difficile stool toxin is detected in 5–20 % of patients with acute exacerbations of ulcerative colitis (UC). There is little data regarding the safety of surgery for UC with concurrent C. difficile. MethodsA retrospective review was performed of 23 patients undergoing colectomy for refractory UC complicated by C. difficile infection between January 2002 and June 2012. Patients were stratified into those who completed a full antibiotic course for C. difficile infection prior to surgery (group A, n = 7) and those who proceeded directly to surgery (group B, n = 16). The primary endpoints of perioperative mortality, ICU requirement, reoperation, readmission, and surgical site infection were assessed within 30 days after surgery. ResultsPostoperatively, no mortalities, ICU admissions, readmission, or reoperations occurred. One group A patient developed a superficial wound infection, which resolved with a course of outpatient antibiotics (14 vs. 0 %, p = 0.12). Average days until return of bowel function and average length of postoperative stay were comparable between group A and B (3.9 vs. 3.6 days, p = 0.70; 7.0 vs. 6.9 days, p = 0.87; respectively). Ninety-one percent of patients subsequently underwent ileal pouch–anal anastomosis. ConclusionColectomy for ulcerative colitis complicated by C. difficile can be performed safely without completing a course of antibiotic therapy.

Infliximab for the treatment of acute exacerbations of ulcerative colitis

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of infliximab for the treatment of acute exacerbations of ulcerative colitis, in accordance with the licensed indication, based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submitted clinical evidence included four randomised controlled trials (RCTs), two comparing infliximab with placebo in patients not responsive to initial treatment with intravenous corticosteroids and one comparing ciclosporin with placebo. A fourth RCT compared ciclosporin with intravenous corticosteroids as the initial treatment after hospitalisation. The manufacturer’s submission concluded that infliximab provides clinical benefit to patients with acute severe, steroid-refractory ulcerative colitis and is well tolerated; it also provides additional clinical benefits over ciclosporin, particularly avoidance of colectomy. A decision tree model was built to compare infliximab with strategies involving ciclosporin, standard care and surgery. After correcting a small number of errors in the model, the revised base-case incremental cost-effectiveness ratio (ICER) for infliximab compared with standard care was £20,000. However, sensitivity analyses revealed considerable uncertainty emanating from the weight of the patient, the timeframe considered and, most importantly, the colectomy rates used. When a more appropriate mix of trials were included in the estimation of colectomy rates, the ICER for infliximab rose to £48,000. The guidance issued by NICE on 31 October 2008 states that infliximab is recommended as an option for the treatment of acute exacerbations of severely active ulcerative colitis only in patients in whom ciclosporin is contraindicated or clinically inappropriate, based on a careful assessment of the risks and benefits of treatment in the individual patient; for people who do not meet this criterion, infliximab should only be used for the treatment of acute exacerbations of severely active ulcerative colitis in clinical trials.

Infliximab for the treatment of acute exacerbations of ulcerative colitis

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of infliximab for the treatment of acute exacerbations of ulcerative colitis, in accordance with the licensed indication, based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submitted clinical evidence included four randomised controlled trials (RCTs), two comparing infliximab with placebo in patients not responsive to initial treatment with intravenous corticosteroids and one comparing ciclosporin with placebo. A fourth RCT compared ciclosporin with intravenous corticosteroids as the initial treatment after hospitalisation. The manufacturer's submission concluded that infliximab provides clinical benefit to patients with acute severe, steroid-refractory ulcerative colitis and is well tolerated; it also provides additional clinical benefits over ciclosporin, particularly avoidance of colectomy. A decision tree model was built to compare infliximab with strategies involving ciclosporin, standard care and surgery. After correcting a small number of errors in the model, the revised base-case incremental cost-effectiveness ratio (ICER) for infliximab compared with standard care was 20,000 pounds. However, sensitivity analyses revealed considerable uncertainty emanating from the weight of the patient, the timeframe considered and, most importantly, the colectomy rates used. When a more appropriate mix of trials were included in the estimation of colectomy rates, the ICER for infliximab rose to 48,000 pounds. The guidance issued by NICE on 31 October 2008 states that infliximab is recommended as an option for the treatment of acute exacerbations of severely active ulcerative colitis only in patients in whom ciclosporin is contraindicated or clinically inappropriate, based on a careful assessment of the risks and benefits of treatment in the individual patient; for people who do not meet this criterion, infliximab should only be used for the treatment of acute exacerbations of severely active ulcerative colitis in clinical trials.

Cost-effectiveness of infliximab for the treatment of acute exacerbations of ulcerative colitis

Infliximab has been shown to be efficacious in acute exacerbations of ulcerative colitis (UC). To evaluate the cost-effectiveness of infliximab treatment in patients hospitalised with acute exacerbations of UC. A decision analysis model was constructed to simulate the progression of acute UC patients treated with infliximab induction regimen over 1 year. Infliximab treatment was compared with standard care, ciclosporin and surgery using transitions derived from infliximab and ciclosporin randomised trials. Costs and outcomes were discounted at 3.5%. Intermediate outcomes of colectomy and post-surgery complications were translated into the primary effectiveness measurement, which was quality-adjusted life years (QALYs) estimated using EQ-5D. One-way and probabilistic sensitivity analyses were performed to estimate the uncertainty around the results. The incremental cost effectiveness ratio (ICER) for infliximab was pound19,545 per QALY compared to ciclosporin, which in turn dominated standard care. Sensitivity analysis indicated patient body weight, utility estimates and treatment effect of alternative treatment strategies to be the most important factors affecting cost-effectiveness. Infliximab induction regimen appears to be a cost-effective treatment option for UC patients hospitalised with an acute exacerbation.